pb2

PB2, a tris(2-carboxyethyl)phosphine (TCEP) analogue, enhances the survival of retinal ganglion cells (RGCs) following axotomy in vitro. Even at nanomolar and picomolar concentrations, PB2 demonstrates pronounced efficacy in promoting RGC survival. Notably, PB2 exhibits superior permeability compared to TCEP. Serving as a potent reducing agent, PB2 provides robust neuroprotection for RGCs[1].

PB28 is a cyclohexylpiperazine derivative that functions as a potent and highly selective agonist of the sigma 2 (σ2) receptor, exhibiting a Ki (binding affinity) of 0.68 nM. At the same time, PB28 acts as an antagonist of the sigma 1 (σ1) receptor, with a Ki of 0.38 nM. PB28 demonstrates a lower affinity for other receptors. It effectively inhibits electrically evoked twitch in both the guinea pig bladder (EC50 value of 2.62 μM) and ileum (EC50 value of 3.96 μM). Moreover, PB28 exhibits the ability to modulate protein-protein interaction between SARS-CoV-2 and human cells. Additionally, PB28 triggers caspase-independent apoptosis and possesses significant antitumor activity.

PP7 is a potent inhibitor of PB1-PB2 interaction(IC50 of 8.6 μM).

σ2 receptor agonist

Methyl brevifolincarboxylate (Brevifolincarboxylic acid methyl ester) is a potent influenza virus PB2 cap-binding inhibitor. Methyl brevifolincarboxylate exhibits inhibitory activity against influenza virus A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/68 (H3N2) with IC50s of 27.16 μM and 33.41 μM. Anti-oxidant activity[1][2]. Methyl brevifolincarboxylate exhibits significant DPPH radical scavenging activity with an IC50 value of 8.9 μM. [1]. Wu QY, et al. Chromatographic fingerprint and the simultaneous determination of five bioactive components of geranium carolinianum L. water extract by high performance liquid chromatography. Int J Mol Sci. 2011;12(12):8740-8749. [2]. Fang SH, et al. Anti-oxidant and inflammatory mediator's growth inhibitory effects of compounds isolated from Phyllanthus urinaria. J Ethnopharmacol. 2008;116(2):333-340.

7-51A is an effective inhibitor of the PB2 subunit of the influenza RNA-dependent RNA polymerase (RdRP), with a dissociation constant (K_D) of 1.64 nM as determined by isothermal titration calorimetry (ITC).

Pimodivir, also known as VX-787, JNJ-872, is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs).

Pimodivir is an inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. The cell-based EC50 for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay. VX-787 is active against a diverse

Pimodivir (VX-787), an influenza A virus polymerases inhibitor via oral, interacts with the viral PB2 subunit.